ISSN

0974-4150 (Online)
0974-4169 (Print)


Author(s): Ganesh Bhawal, Meenakshi Deodhar, Ashok Bhosale, Deepak Lande

Email(s): ganesh_bhawal@rediffmail.com

DOI: Not Available

Address: Ganesh Bhawal*, Meenakshi Deodhar, Ashok Bhosale and Deepak Lande
Department of Pharmaceutical Chemistry, S.G.R.S College of Pharmacy, Saswad, Pune, Maharashtra 413716, India
*Corresponding Author

Published In:   Volume - 3,      Issue - 4,     Year - 2010


ABSTRACT:
The present work relates to novel phenothiazines derivatives as antipsychotic agents. The introduction of the Chlorpromazine (a Phenothiazine class drug) in 1952 was positive advance in the treatment of psychosis. Phenothiazines constitute one of the most active classes of compounds possessing diversified biological applications and are the most commonly used class of antipsychotic agents. Phenothiazines mainly act by antagonism of the D2 receptors and are thus useful for the treatment of the positive symptoms and have very little effect on negative symptoms or cognitive deficits In addition, blockade of dopamine D2 receptors leads to an increase in prolactin secretion and associated neuroendocrine disorders including gynecomastia, amenorrhea, and sexual dysfunction. The antipsychotic efficacy of typical neuroleptics is related to the D2 receptor blockade. D2 receptor is one of the G protein coupled receptors family that also includes the D3 and D4 receptor subtypes. And it was found that the D4 receptor density is elevated in schizophrenia. About six fold increases in the D4 receptor subtype have been reported in schizophrenic brains, compared with normals. Autoradiographic analyses with the D4 selective ligand 3H-NGD 94-1 show D4 sites to be dense in rat and human hippocampus, hypothalamus, and neocortex, among other brain regions, and to be absent in the striatum. These findings suggested that a D4-specific compound might treat schizophrenia as effectively as Clozapine but without the D2 antagonist-mediated EPS or the Clozapine constellation of side effects. We undertook a plan of building pyrazoline ring fused with the nucleus of phenothiazine. The preliminary pharmacological screening of the synthesized compounds revealed that out of the 12 compounds synthesized 6 compound (3a,3c,3d,3f,3j,3l) displayed significant activity.


Cite this article:
Ganesh Bhawal, Meenakshi Deodhar, Ashok Bhosale, Deepak Lande. Design, Synthesis and Evaluation of Novel Phenothiazines as Antipsychotic Agents.. Asian J. Research Chem. 3(4): Oct. - Dec. 2010; Page 906-910.


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